N6-methyladenosine in Flaviviridae viral RNA genomes regulates infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE83438 | GEO | 2016/10/21
SECONDARY ACCESSION(S): PRJNA325928
REPOSITORIES: GEO
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Project description:The modification N6-methyladenosine (m6A) affects rates of translation and degradation of mRNA transcripts. We analyzed m6A across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV) using MeRIP-seq. We used the uninfected replicates, among which we would expect little biological variation in methylation, as negative controls to validate statistical methods for the detection of m6A changes in MeRIP-seq data. Applying validated statistical methods, we found that innate immune response to Flaviviridae viruses alters m6A modification of specific cellular transcripts compared to uninfected controls. Finally, we find that these changes in m6A can in turn affect splicing or translation of genes relevant to infection.
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Project description:The RNA modification N6-methyladenosine (m6A) can modulate mRNA fate and thus affect many biological processes. We analyzed m6A modification across the transcriptome following infection by dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and hepatitis C virus (HCV). We found that infection by these viruses in the Flaviviridae family alters m6A modification of specific cellular transcripts, including RIOK3 and CIRBP. During viral infection, the addition of m6A to RIOK3 promotes its translation, while loss of m6A in CIRBP promotes alternative splicing. Importantly, we found that viral activation of innate immune sensing or the endoplasmic reticulum (ER) stress response contributes to the changes in m6A modification in RIOK3 and CIRBP, respectively. Further, several transcripts with infection-altered m6A profiles, including RIOK3 and CIRBP, encode proteins that influence DENV, ZIKV, and HCV infection. Overall, this work reveals that cellular signaling pathways activated during viral infection lead to alterations in m6A modification of host mRNAs to regulate infection.
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